RESUMEN
When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.
RESUMEN
OBJECTIVE: The aim of this case series was to demonstrate that surgical tracheostomy can be undertaken safely in critically ill mechanically ventilated patients with coronavirus disease 2019 (COVID-19) and that it is an effective weaning tool. STUDY DESIGN: Retrospective case series. SETTING: Single academic teaching hospital in London. METHODS: All adult patients admitted to the adult intensive care unit (AICU), diagnosed with severe COVID-19 infection and requiring surgical tracheostomy between the March 10, 2020, and May 1, 2020, were included. Data collection focused upon patient demographics, AICU admission data, tracheostomy-specific data, and clinical outcomes. RESULTS: Twenty patients with COVID-19 underwent surgical tracheostomy. The main indication for tracheostomy was to assist in respiratory weaning. Patients had undergone mechanical ventilation for a median of 16.5 days prior to surgical tracheostomy. Tracheostomy remained in situ for a median of 12.5 days. Sixty percent of patients were decannulated at the end of the data collection period. There were no serious immediate or short-term complications. Surgical tracheostomy facilitated significant reduction in intravenous sedation at 48 hours after tracheostomy formation. There was no confirmed COVID-19 infection or reported sickness in the operating surgical or anesthetic teams. CONCLUSION: Surgical tracheostomy has been demonstrated to be an effective weaning tool in patients with severe COVID-19 infection.
RESUMEN
Mammals, including humans, prepare for sleep by nesting and/or curling up, creating microclimates of skin warmth. To address whether external warmth induces sleep through defined circuitry, we used c-Fos-dependent activity tagging, which captures populations of activated cells and allows them to be reactivated to test their physiological role. External warming tagged two principal groups of neurons in the median preoptic (MnPO)/medial preoptic (MPO) hypothalamic area. GABA neurons located mainly in MPO produced non-rapid eye movement (NREM) sleep but no body temperature decrease. Nitrergic-glutamatergic neurons in MnPO-MPO induced both body cooling and NREM sleep. This circuitry explains how skin warming induces sleep and why the maximal rate of core body cooling positively correlates with sleep onset. Thus, the pathways that promote NREM sleep, reduced energy expenditure, and body cooling are inextricably linked, commanded by the same neurons. This implies that one function of NREM sleep is to lower brain temperature and/or conserve energy.
